CIML-NK Cells for Acute Myeloid Leukemia

Overseen By Caitlin Cottrell

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Prednisone, Investigational therapies

Disqualifiers: CNS disease, APML, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether a new cell therapy, called Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK), can safely treat acute myeloid leukemia (AML) that has returned or is unresponsive to treatment. These specialized cells, derived from a donor, are designed to target and fight cancer cells in the patient's body. This therapy suits patients with AML in their bone marrow who have not responded to initial treatments. Participants must have a related donor available to provide the necessary cells. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who are taking more than 10mg of prednisone (a type of steroid) daily or more than 0.5mg/kg of prednisone daily. It also excludes those on other investigational treatments.

Is there any evidence suggesting that cytokine-induced memory-like natural killer cells are likely to be safe for humans?

In a previous study, researchers found that cytokine-induced memory-like natural killer cells (CIML-NK) could be safely created from donor cells and administered to patients. These cells are designed to fight cancer more effectively. Studies have shown that CIML-NK cells can target and attack leukemia cells without causing severe side effects. Some patients experienced mild reactions, such as fever or chills, but these were manageable. As this treatment is in early trials, researchers continue to closely monitor its safety. Early results appear promising, but more research is needed to fully understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Cytokine-Induced Memory-Like Natural Killer (CIML-NK) cells for treating Acute Myeloid Leukemia (AML) because they offer a new approach compared to standard treatments like chemotherapy and targeted therapies. Unlike traditional treatments, which often target cancer cells directly, CIML-NK cells harness the body's immune system to fight cancer. These cells are derived from a donor and are engineered to remember and attack cancer cells more effectively. This innovative method could potentially lead to more durable responses and fewer side effects, making it a promising option for patients with AML.

What evidence suggests that CIML-NK cells might be an effective treatment for acute myeloid leukemia?

Research has shown that cytokine-induced memory-like natural killer cells (CIML-NK) could be promising for treating acute myeloid leukemia (AML). These specially activated cells excel at attacking leukemia cells and sending crucial signals to the immune system. Studies have found that CIML-NK cells effectively target both lab-grown leukemia cells and those from patients. Importantly, earlier trials found that these cells usually do not cause severe graft-versus-host disease, a common concern with cell-based treatments. Overall, these findings suggest that CIML-NK cells could be a strong treatment option for AML that has returned or is not responding to other treatments. Participants in this trial will receive the CIML-NK cell treatment to further evaluate its effectiveness and safety. ^{2 4 5 6 7}

Who Is on the Research Team?

Zahra Hudda

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

Adults diagnosed with relapsed or refractory acute myeloid leukemia (AML) who have a compatible family donor can join this trial. They must have at least 5% AML cells in their bone marrow and be able to perform daily activities at least half of the time. People with certain heart, lung, liver issues, uncontrolled infections, or on high-dose steroids cannot participate.

Inclusion Criteria

My leukemia did not respond well to initial treatments.

I am 12 years old or older.

I have a closely related donor who is a partial genetic match for me.

Exclusion Criteria

My heart's pumping ability is below 45%.

Pulmonary Function: Oxygen saturation <92% on room air

Known allergy or hypersensitivity reaction to IL-2 injections

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive a lymphodepleting chemotherapy regimen to prepare for CIML-NK cell infusion

1-2 weeks

CIML-NK Cell Infusion

Cytokine-induced memory-like NK cells are infused into participants

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after CIML-NK cell infusion

4 weeks

4 visits (in-person)

Long-term Follow-up

Participants are assessed for clinical response and ability to proceed to hematopoietic stem cell transplant

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK)

Trial Overview The study is testing if natural killer cells treated with cytokines from a relative's donated cells are safe and effective for treating AML that has come back or hasn't responded to other treatments.

How Is the Trial Designed?

Group I: Cytokine-Induced Memory-Like Natural Killer (CIML-NK) Cells Experimental Treatment 1 Intervention

The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product.

Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) is already approved in United States for the following indications:

Approved in United States as CIML-NK cells for:

• Relapsed or refractory acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

Cytokine-induced memory-like (CIML) NK cells, which are generated through brief stimulation with IL-12, IL-15, and IL-18, show enhanced effector functions and long-term persistence, making them promising candidates for cancer immunotherapy.

Clinical trials have demonstrated that infusions of CIML NK cells are safe and have led to complete clinical remissions in patients with relapse/refractory acute myeloid leukemia (AML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. Terrén, I., Orrantia, A., Astarloa-Pando, G., et al.[2022]

Cytokine-induced killer (CIK) cells can be successfully expanded from patients with acute leukemia, showing a median of 35.3% CD3(+)CD56(+) cells that are effective in killing certain leukemia cells, particularly acute myeloid leukemia (AML) targets.

The study indicates that CIK cells have potential for immunotherapy in AML, as they can effectively target both autologous and allogeneic leukemia cells, suggesting their use in various treatment scenarios, including post-transplant relapses and chemotherapy-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Linn, YC., Lau, LC., Hui, KM.[2022]

Cytokine-induced killer (CIK) cells, derived from patients or healthy donors, show strong potential in targeting leukemia cells without harming normal hematopoietic stem cells, making them a promising option for leukemia treatment.

CIK cells can generate a graft versus tumor response while minimizing graft versus host disease, suggesting they could effectively prevent leukemia relapse after hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia. Yang, XY., Zeng, H., Chen, FP.[2020]

In a study involving 24 patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), the infusion of autologous cytokine-induced killer (CIK) cells did not show a survival benefit for AML patients post-transplant, nor did it significantly reduce detectable disease in CML patients.

The treatment was found to be safe, with only mild adverse reactions like fever reported, but the results suggest that further modifications to enhance the effectiveness of CIK cells are necessary for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission. Linn, YC., Yong, HX., Niam, M., et al.[2022]

Cytokine-induced killer (CIK) cells, derived from patients with acute myeloid leukemia (AML), show strong cytotoxicity against both autologous and allogeneic leukemia cells, making them a promising option for targeted leukemia therapy.

CIK cells do not induce graft-versus-host disease in mouse models, suggesting they can be safely used in transplants, and their infusion has been shown to prolong survival in leukemia-bearing mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Linn, YC., Hui, KM.[2019]

In a clinical trial involving 15 patients with relapsed/refractory acute myeloid leukemia (AML), the use of donor-derived memory-like (ML) NK cells combined with N-803 (an IL-15 superagonist) was well tolerated and resulted in an impressive 87% of patients achieving a composite complete response within 28 days.

The ML NK cells showed significant expansion and persistence, remaining the dominant lymphocyte population for over 2 months post-transplant, and exhibited enhanced antitumor functions compared to conventional NK cells, indicating their potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Berrien-Elliott, MM., Foltz, JA., Russler-Germain, DA., et al.[2023]

Cytokine-induced memory-like NK cells show enhanced ability to produce interferon-γ and kill leukemia cells, making them a promising option for treating acute myeloid leukemia (AML).

In a first-in-human phase 1 clinical trial, memory-like NK cells were successfully expanded in AML patients, leading to clinical responses in five out of nine patients, including four complete remissions, indicating their potential effectiveness as an immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Romee, R., Rosario, M., Berrien-Elliott, MM., et al.[2021]

Natural killer (NK) cell-based immunotherapy shows promise in treating acute myeloid leukemia (AML) by targeting cancer cells and enhancing the immune response, particularly through the use of cytokine-induced memory-like (CIML) NK cells.

CIML-NK cells, which are pre-activated with specific cytokines, demonstrate a longer lifespan and adaptive immunity characteristics, making them a potentially effective and safe treatment option for AML, addressing the limitations of traditional NK cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. Bakhtiyaridovvombaygi, M., Yazdanparast, S., Mikanik, F., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5436500/

Cytokine-induced memory-like natural killer cells exhibit ... We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223015160

Review Cytokine‐Induced Memory‐Like NK Cells This review highlights the current application, challenges, and opportunities of CIML-NK cell-based therapy in AML.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01898793

NCT01898793 | Cytokine-induced Memory-like NK Cells in ... This phase I/2 trial studies the side effects and best dose of activated natural killer cells in treating patients with relapsed or refractory acute myeloid ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03068819

NCT03068819 | Cytokine Induced Memory-like NK Cell ... The use of CIML NK cells is unlikely to lead to excessive graft versus host disease (GVHD) as previous studies have not been associated with excessive GVHD ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.884648/full

Cytokine-Induced Memory-Like NK Cells: From the Basics ... We summarize the current knowledge about memory-like NK cells, focusing on IL-12/15/18-induced memory-like NK cells, and discuss their properties and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05580601

Cytokine-Induced Memory-Like Natural Killer Cells (CIML ... The objective of this study is to demonstrate that cytokine-induced memory-like natural killer cells can be generated from donor cells and infused safely into ...

7. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/CIML-NK

Cytokine-Induced Memory-Like Natural Killer Cells (CIML ... Peripheral blood from a related haploidentical donor will be collected for the isolation of natural killer (NK) cells. NK cells will be induced into a memory- ...